A Review of the Lipid Metabolism Reprogramming in Tumor Associated Macrophages

ZHAO Kun, SHI Rong-chen, MIAO Hong-ming


Tumor associated macrophages (TAMs) are one of the most common types of stromal cells in solid tumors. They are closely related to the immunosuppressive status of tumor microenvironment and potentiate the malignant progress of tumors. Studies have shown that metabolism in tumor associated macrophages has been reprogrammed and involved in the regulation of their own polarization and corresponding functions and phenotypes. Metabolic reprogramming refers to the alteration of key enzymes activity, substrate and its associated metabolites’ concentration in a certain metabolic pathway, which accounts for the disorder of original metabolic states. In this paper, we mainly concentrated on the lipid metabolic reprogramming of TAMs, including triglycerides, fatty acids and their derivatives, cholesterol, phospholipids, and their regulations on tumor progression. However, the metabolism of tumor and tumor microenvironment cells is highly heterogeneous. It is worthy of further exploration on the similarities and differences of lipid metabolism reprogramming between stromal cells and tumor cells, and the mechanism of how reprogramming modulates cell activity. It will be a new strategy for immunotherapy of tumor with metabolic intervention to accurately target the lipid metabolism reprogramming of TAMs, so as to promote the polarization of TAMs to M1 like macrophages, when synthetically considering the diverse types of tumors and different stages of development.


Keywords: Tumor associated macrophages, Immunosuppression, Lipid metabolism reprogramming, Tumor progression


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VITALE I, MANIC G, COUSSENS L M, et al. Macrophages and metabolism in the tumor microenvironment. Cell Metab,2019,30(1): 36–50.

MEHLA K, SINGH P K. Metabolic regulation of macrophage polarization in cancer. Trends Cancer,2019,5(12): 822–834.

RABOLD K, NETEA M G, ADEMA G J, et al. Cellular metabolism of tumor-associated macrophages—functional impact and consequences. FEBS Lett,2017,591(19): 3022–3041.

DENARDO D G, RUFFELL B. Macrophages as regulators of tumour immunity and immunotherapy. Nat Rev Immunol,2019,19(6): 369–382. SHANG S, JI X, ZHANG L, et al. Macrophage ABHD5 suppresses NFkappaB-dependent matrix metalloproteinase expression and cancer metastasis. Cancer Res,2019,79(21): 5513–5526.

MIAO H, OU J, PENG Y, et al. Macrophage ABHD5 promotes colorectal cancer growth by suppressing spermidine production by SRM. Nat Commun, 2016, 7: 11716[2020-11-03]. https://www.nature.com/articles/ncomms11716. doi: 10.1038/ncomms11716.

XIANG W, SHI R, KANG X, et al. Monoacylglycerol lipase regulates cannabinoid receptor 2-dependent macrophage activation and cancer progression. Nat Commun,2018,9(1): 2574–2586.

OU J, MIAO H, MA Y, et al. Loss of ABHD5 promotes colorectal tumor development and progression by inducing aerobic glycolysis and epithelial-mesenchymal transition. Cell Rep,2014,9(5): 1798–1811.

SU P, WANG Q, BI E, et al. Enhanced lipid accumulation and metabolism are required for the differentiation and activation of tumor-associated macrophages. Cancer Res,2020,80(7): 1438–1450.

VATS D, MUKUNDAN L, ODEGAARD J I, et al. Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation. Cell Metab,2006,4(1): 13–24.

MARÉCHAL L, LAVIOLETTE M, RODRIGUE-WAY A, et al. The CD36-PPARγ pathway in metabolic disorders. Int J Mol Sci,2018,19(5): 1529–1544.

WU L, ZHANG X, ZHENG L, et al. RIPK3 orchestrates fatty acid metabolism in tumor-associated macrophages and hepatocarcinogenesis. Cancer Immunol Res,2020,8(5): 710–721.

DENG X, ZHANG P, LIANG T, et al. Ovarian cancer stem cells induce the M2 polarization of macrophages through the PPARgamma and NF-kappaB pathways. Int J Mol Med,2015,36(2): 449–454.

ZHANG Q, WANG H, MAO C, et al. Fatty acid oxidation contributes to IL-1β secretion in M2 macrophages and promotes macrophage-mediated tumor cell migration. Mol Immunol, 2018, 94: 27-35[2020-11-03]. https://pubmed.ncbi.nlm.nih.gov/29248877/. doi: 10.1016/j.molimm. 2017.12.011.

ZELENAY S, VAN DER VEEN A G, BÖTTCHER J P, et al. Cyclooxygenase-dependent tumor growth through evasion of immunity. Cell,2015,162(6): 1257–1270.

CEN B, LANG J D, DU Y, et al. Prostaglandin E2 induces miR675-5p to promote colorectal tumor metastasis via modulation of p53 expression. Gastroenterology, 2020, 158(4): 971–984.e10[2020-11-03]. https://pubmed. ncbi.nlm.nih.gov/31734182/. doi: 10.1053/j.gastro.2019.11.013.

WANG D, DUBOIS R N. Role of prostanoids in gastrointestinal cancer. J Clin Invest,2018,128(7): 2732–2742.

FENG M, JIANG W, KIM B Y S, et al. Phagocytosis checkpoints as new targets for cancer immunotherapy. Nature Reviews Cancer,2019,19(10): 568–586.

PRIMA V, KALIBEROVA L N , KALIBEROV S, et al. COX2/mPGES1/PGE2 pathway regulates PD-L1 expression in tumor- associated macrophages and myeloid-derived suppressor cells. Proc Natl Acad Sci U S A,2017,114(5): 1117–1122.

BIANCHINI F, MASSI D, MARCONI C, et al. Expression of cyclo-oxygenase-2 in macrophages associated with cutaneous melanoma at different stages of progression. Prostaglandins Other Lipid Mediat,2007, 83(4): 320–328.

RINGLEB J, STRACK E, ANGIONI C, et al. Apoptotic cancer cells suppress 5-lipoxygenase in tumor-associated macrophages. J Immunol, 2018,200(2): 857–868.

DAURKIN I, ERUSLANOV E, STOFFS T, et al. Tumor-associated macrophages mediate immunosuppression in the renal cancer microenvironment by activating the 15-lipoxygenase-2 pathway. Cancer Res,2011,71(20): 6400–6409.

MCKILLOP I H, GIRARDI C A, THOMPSON K J. Role of fatty acid binding proteins (FABPs) in cancer development and progression. Cell Signal, 2019, 62: 109336[2020-11-03]. https://pubmed.ncbi.nlm.nih. gov/31170472/. doi: 10.1016/j.cellsig.2019.06.001.

ELSHERBINY M E, EMARA M, GODBOUT R. Interaction of brain fatty acid-binding protein with the polyunsaturated fatty acid environment as a potential determinant of poor prognosis in malignant glioma. Prog Lipid Res,2013,52(4): 562–570.

ZHANG Y, SUN Y, RAO E, et al. Fatty acid-binding protein E-FABP restricts tumor growth by promoting IFN-β responses in tumor-associated macrophages. Cancer Res,2014,74(11): 2986–2998.

RAO E, SINGH P, ZHAI X, et al. Inhibition of tumor growth by a newly-identified activator for epidermal fatty acid binding protein. Oncotarget,2015,6(10): 7815–7827.

HAO J, YAN F, ZHANG Y, et al. Expression of adipocyte/macrophage fatty acid-binding protein in tumor-associated macrophages promotes breast cancer progression. Cancer Res,2018,78(9): 2343–2355.

VAN DER VORST E P C, THEODOROU K, WU Y, et al. High-density lipoproteins exert pro-inflammatory effects on macrophages via passive cholesterol depletion and PKC-NF-kappaB/STAT1-IRF1 signaling. Cell Metab,2017,25(1): 197–207.

GOOSSENS P, RODRIGUEZ-VITA J, ETZERODT A, et al. Membrane cholesterol efflux drives tumor-associated macrophage reprogramming and tumor progression. Cell Metab, 2019, 29(6): 1376−1389.e4[2020-11-03]. https://pubmed.ncbi.nlm.nih.gov/30930171/. doi: 10.1016/j.cmet.2019. 02.016.


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